I. Field of the Invention
The present invention relates generally to the fields of oncology, molecular biology, and medicine. More particularly, the invention relates to use of certain miRNAs that are dysregulated in so-called “triple-negative” breast cancer as both diagnostic and therapeutic targets.
II. Description of Related Art
MicroRNAs (miRNAs) are small RNA molecules, 19-25 nucleotides in length. miRNAs are not translated, instead they serve as regulators of mRNA expression (Ouellet et al., 2006). For the most part, miRNAs bind to complementary regions in target mRNA 3′UTRs and either cause mRNA degradation or prevent its translation (Engels and Hutvagner, 2006). Generally, one observes a decrease of the target at the protein level; however, there is some emerging evidence that miRNAs can also cause upregulation of their targets. Individual miRNAs have been found to be expressed in cell-specific manner, at specific developmental stages, as well as differentially expressed in disease states (Yi et al., 2008; Sempere et al., 2007). Importantly, miRNAs have been implicated as playing roles as oncogenes and tumor suppressors (Cho, 2007; Cowland et al., 2007). While there are miRNAs that are found to be overexpressed in cancers, many appear to be lost and they tend to localize to fragile sites (Calin et al., 2004).
Breast cancer is a heterogeneous disease which can be grouped into several different subtypes. One of the most well-differentiated subtypes is Luminal A, which encompasses cancers that retain their hormone receptors (estrogen and progesterone receptors). On the other end of the spectrum, there is the triple-negative (TN)/basal subtype. TN cancers have lost expression of their hormone receptors and do not overexpress HER2/neu. TN breast cancers are poorly-differentiated, have often undergone epithelial to mesenchymal transition (EMT) and have poor a prognosis. Thus, improved methods to distinguish these types of cancers at early stages are urgently needed.